1. Field of the Invention
The present invention generally relates to a microfluidic device and a manufacturing method thereof. More particularly, the present invention relates to a microfluidic device with at least a capillary having dead-volume free interface therebetween.
2. Description of Related Art
Since the concept of miniaturized total analysis systems are developed, a great number of microfluidic devices have been demonstrated for a variety of applications. Common analytical assays including polymerase chain reaction (PCR), DNA analyses and sequencing, protein separations, immunoassay, and intra- and inter-cellular analysis have been reduced in size and fabricated in a chip. The reduction in the size of the analytical processes has many advantages including rapid analysis, less sample amount, and smaller size.
Although there have been many successes, an important hurdle that still needs to be cleared is the connection between the micro-components of a device and the macro-environment of the world. This part of the device is often referred to as the macro-to micro interface. The difficulty results from the fact that samples and reagents are typically transferred in quantities of microliters to milliliters whereas microfluidic devices consume only nanoliters or picoliters of samples due to the size of reaction chambers and channels, which have dimensions on the order of microns.
Electrospray mass spectrometry is usually used to analyze or identify proteins or DNAs. The method for linking a microchip device and an electrospray tip, such as a fused silica capillary, has been disclosed in several prior art references. For example, “A Microfabricated Device for Rapid Protein Identification by Microelectrospray Ion Trap Mass Spectrometry”, Anal. Chem., 1997, 69, 3153-3160; “Microfabricated Devices for Capillary Electrophoresis-Electrospray Mass Spectrometry”, Anal. Chem., 1999, 71, 3258-Volume”, Anal. Chem., 1999, 71, 3292-3296; “Development of Multichannel Devices with an Array of Electrospray Tips for High-Throughput Mass Spectrometry”, Anal. Chem., 2000, 72, 3303-3310. In the references, a dead-volume interface will be formed between the electrospray tip and the microchip device after connecting or linking the electrospray tip to the microchip device.
In order to resolve the problem of dead-volume interface between the electrospray tip and the microchip device, some methods are provided in several prior art references, such as “Polymer Microspray with an Integrated Thick-Film Microelectrode”, Anal. Chem., 2001, 73, 5353-5357; “Microfabricated polymer injector for direct mass spectrometry coupling”, Proteomics 2002, 2, 405-412; “Microfabrication of polydimethylsiloxane electrospray ionization emitters”, Journal of Chromatography A, 924 (2001) 137-145; “An Electrospray Ionization Source for Integration with Microfluidics”, Anal. Chem., 2002, 74, 5897-5901; “A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry”, Anal. Chem., 2000, 72, 4058-4063; “A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry”, Anal. Chem., 2000, 72, 4058-4063; “Polymer-based electrospray chips for mass spectrometry”, The 12th IEEE International Conference on Micro Electro Mechanical Systems (MEMS '99), Orlando, Fla., 1999, pp. 523-528 (it is also filed a patent of WO00/30167); “A planar on-chip micro-nib interface for NanoESI-MS microfluidic applications”, J. Micromech. Microeng. 14 (2004) 310-316; and “Minimal dead-volume connectors for microfluidics using PDMS casting techniques”, J. Micromech. Microeng., 14 (2004) 1484-1490. However, these methods disclosed in the above prior references have disadvantages of complex, time consuming and high cost.
In addition, the methods described about the micro-fabricated electrospray and electrospray nozzle have been disclosed in U.S. Pat. Nos. 5,994,696, 6,459,080, 6,417,510, 6,858,842, 6,800,202, 6,723,984, 6,673,253, WO 00/30167 and U.S. Pat. No. 5,145,565, the teachings of which are incorporated herein by reference.